Novel clustering of sodium channel Na_v1.1 with ankyrin-G and neurofascin at discrete sites in the inner plexiform layer of the retina

Voltage-gated sodium channels cluster at sites of action potential generation and propagation by interacting with partner proteins such as neurofascin, an adhesion molecule in the L1 family, and ankyrin-G, a spectrin-binding protein required for sodium channel accumulation at axon initial segments. Here, we describe in the inner plexiform layer of the retina a novel site of high-density sodium channel clustering, marked by ankyrin-G and neurofascin. The sodium channel isoform at this site is Na_v1.1, instead of the Na_v1.6 channels more commonly found in association with the clustering machinery. During development, Na_v1.2 channels first associate with ankyrin-G in the inner plexiform layer but are later replaced by Na_v1.1, similar to the switch from Na_v1.2 to Na_v1.6 at nodes of Ranvier and initial segments. This represents the first instance of high-density clustering of Na_v1.1 channels, which may contribute to synaptic interactions among retinal neurons in the inner plexiform layer.